Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing - Implication for metabolic remodeling.
Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing - Implication for metabolic remodeling.
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通过转座子测序对胞内分枝杆菌中的必需基因进行全基因组鉴定 - 对代谢重塑的影响。
DOI：
10.1038/s41598-020-62287-2
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Matsumoto S.
中科院分区：
文献类型：
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作者：
Tateishi Y;Minato Y;Baughn AD;Ohnishi H;Nishiyama A;Ozeki Y;Matsumoto S.
人类非结核分枝杆菌（NTM）病的全球发病率正在迅速上升。然而，在最佳生长条件和与NTM自然生态相关的条件下，如缺氧，基因必要性的知识缺乏。在这项研究中，我们利用转座子测序来全面鉴定细胞内分枝杆菌生长所必需的基因。在5126个基因中。胞内atcc13950、506个基因被鉴定为必需基因，其中与m的必需基因共有280个、158个基因。tuberculosisandM。分别marinum。共享基因包括现有抗结核药物的靶基因，包括SQ109，其靶向海藻糖单菌酸转运体MmpL3。在缺氧条件下适应性降低的175个基因中，提示在缺氧条件下优先进行糖异生、乙醛酸循环和琥珀酸盐生成等碳水化合物代谢。包括蛋白酶体系统和真菌硫醇氧化还原系统在内的毒力相关基因也被确定为缺氧条件下的条件必需基因，与这些抑制剂存在的有氧条件相比，在缺氧条件下对细菌生长的抑制更有效，这进一步支持了这一点。本研究全面确定了m生长所必需的功能。在与宿主环境相关的条件下在细胞内发生。这些发现为药物发现提供了关键的功能基因组信息。
The global incidence of the human nontuberculous mycobacteria (NTM) disease is rapidly increasing. However, knowledge of gene essentiality under optimal growth conditions and conditions relevant to the natural ecology of NTM, such as hypoxia, is lacking. In this study, we utilized transposon sequencing to comprehensively identify genes essential for growth inMycobacterium intracellulare. Of 5126 genes ofM. intracellulareATCC13950, 506 genes were identified as essential genes, of which 280 and 158 genes were shared with essential genes ofM. tuberculosisandM. marinum, respectively. The shared genes included target genes of existing antituberculous drugs including SQ109, which targets the trehalose monomycolate transporter MmpL3. From 175 genes showing decreased fitness as conditionally essential under hypoxia, preferential carbohydrate metabolism including gluconeogenesis, glyoxylate cycle and succinate production was suggested under hypoxia. Virulence-associated genes including proteasome system and mycothiol redox system were also identified as conditionally essential under hypoxia, which was further supported by the higher effective suppression of bacterial growth under hypoxia compared to aerobic conditions in the presence of these inhibitors. This study has comprehensively identified functions essential for growth ofM. intracellulareunder conditions relevant to the host environment. These findings provide critical functional genomic information for drug discovery.